Inverse associations between serum levels of secreted frizzled-related protein-5 (SFRP5) and multiple cardiometabolic risk factors: KORA F4 study

Abstract

AimsSecreted frizzled-related protein (Sfrp)5 has beneficial effects on insulin sensitivity, inflammation and cardiovascular risk in different mouse models, but its relevance for cardiometabolic diseases in humans is controversial. We aimed to characterise associations of circulating SFRP5 with cardiometabolic risk factors and prediabetes/type 2 diabetes in a large population-based cohort.MethodsCross-sectional associations between serum SFRP5 and cardiometabolic risk factors as well as prediabetes/type 2 diabetes were investigated in 1096 participants aged 62–81 years from the German KORA F4 study, of whom 666 had prediabetes or type 2 diabetes. Multivariable linear regression models were adjusted for potential confounders including age, sex, body mass index (BMI), lifestyle factors, lipids, hypertension, kidney function and myocardial infarction.ResultsHigher serum SFRP5 levels were associated with lower HbA1c, BMI, systolic blood pressure, estimated glomerular filtration rate and high-sensitivity C-reactive protein levels and with higher levels of high-density lipoprotein cholesterol and adiponectin in the fully adjusted model (all P < 0.009). In contrast, favourable associations between SFRP5 and glycaemia, insulin, insulin resistance and other cardiometabolic risk factors were attenuated after adjustment for BMI. Serum SFRP5 levels were lower in participants with prediabetes or type 2 diabetes [(median (25th; 75th percentile) 48.8 (35.5; 65.7) ng/ml] compared to participants with normal glucose tolerance [55.9 (42.6; 69.6) ng/ml] (P < 0.001). In the fully adjusted model, higher SFRP5 was associated with lower odds of prediabetes/type 2 diabetes [OR (95% CI) (0.72 (0.58; 0.89)) per doubling of SFRP5, P < 0.01].ConclusionsHigher serum SFRP5 was inversely associated with multiple risk factors for type 2 diabetes and cardiovascular diseases. However, BMI represents a strong confounder of some of these associations. Higher circulating SFRP5 was also associated with lower odds of prediabetes/type 2 diabetes, and this association was independent of BMI. Thus, SFRP5 emerges as novel biomarker that merits further research in the context of prevention of cardiometabolic diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-017-0591-x) contains supplementary material, which is available to authorized users.

Research update on the association between SFRP5, an anti‐inflammatory adipokine, with obesity, type 2 diabetes mellitus and coronary heart disease

“…Hu ZP et al 36 found that circulating plasma concentrations of SFRP5 were decreased in T2DM patients compared with healthy controls and they were negatively correlated with homeostasis model assessment of insulin resistance, suggesting that SFRP5 might exert a protective effect on the mechanism of T2DM. Similar results were observed by clinical studies conducted by Hu WJ et al, 38 Cheng et al 48 and Carstensen-Kirberg et al, 49…”

“…Hu ZP et al found that circulating plasma concentrations of SFRP5 were decreased in T2DM patients compared with healthy controls and they were negatively correlated with homeostasis model assessment of insulin resistance, suggesting that SFRP5 might exert a protective effect on the mechanism of T2DM. Similar results were observed by clinical studies conducted by Hu WJ et al, Cheng et al and Carstensen‐Kirberg et al, and all indicated a possible role for SFRP5 as a protective factor in the pathogenesis of T2DM. In contrast, Canivell et al observed that circulating plasma levels of SFRP5 were augmented in patients with T2DM compared with prediabetic patients and healthy controls.…”

Myeloperoxidase, superoxide dismutase‐3, cardiometabolic risk factors, and distal sensorimotor polyneuropathy: The KORA F4/FF4 study

“…The measurement of serum lipids was done as described, the assessment of kidney function from the estimated glomerular filtration rate (eGFR) was based on the chronic kidney disease epidemiology creatinine equation.…”

“…Measurement methods of glucose, insulin and HbA 1c , and calculation of the homeostasis model assessment of insulin resistance (HOMA-IR) and whole-body insulin sensitivity index (composite) were also reported before. [27][28][29] The measurement of serum lipids was done as described, 27,30 the assessment of kidney function from the estimated glomerular filtration rate (eGFR) was based on the chronic kidney disease epidemiology creatinine equation.…”

Remodeling adipose tissue inflammasome for type 2 diabetes mellitus treatment: Current perspective and translational strategies

“…Secreted frizzled protein‐5 (SFP5) is secreted from various tissues including visceral, subcutaneous, pericardial adipose tissues, liver, heart, pancreatic islets, and mononuclear blood cells . Different cross‐sectional clinical studies have found that SFP5 serum levels are inversely related to diabetes and cardiovascular disease risk factors, and its concentration is lower in prediabetes or T2DM . Treatment with Liraglutide increased SFP5 levels .…”